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Nat Commun. 2016 Jan 28;7:10421. doi: 10.1038/ncomms10421.

The occurrence of intracranial rhabdoid tumours in mice depends on temporal control of Smarcb1 inactivation.

Author information

1
Institut Curie, Paris Sciences et Lettres Research University, InsermU830, Laboratoire de Genetique et Biologie des Cancers, 26 rue d'Ulm, 75005 Paris, France.
2
SiRIC- Institut Curie, Laboratoire de Recherche Translationnelle en Oncologie Pédiatrique, 26 rue d'Ulm, 75005 Paris, France.
3
Département de Biologie des Tumeurs, Institut Curie, Service d'anatomie pathologique, 26 rue d'Ulm, 75005 Paris, France.
4
Institut Bergonie, Institut Curie, Unité de génétique somatique, Département de Biologie des Tumeurs, 26 rue d'Ulm, 75005 Paris, France.
5
Institut Curie, Plateforme de pathologie expérimentale, Département de Biologie des Tumeurs, 26 rue d'Ulm, 75005 Paris, France.
6
Centre Léon Bérard, Departement de Biopathologie, 28 Promenade Léa et Napoléon Bullukian, 69008 Lyon, France.
7
Departement de neuropathology, Hopital Sainte-Anne, 1 rue Cabanis, 75014 Paris, France.
8
Université Paris Descartes, 75006 Paris, France.
9
Service de neurochirurgie pédiatrique, Hopital Necker, 149 rue de Sèvres, 75015 Paris, France.
10
Institut Curie, Paris Sciences et Lettres University Research, CNRS UMR 3306, INSERM U1005, Centre Universitaire d'Orsay, 91898 Orsay, France.
11
Département d'oncologie pédiatrique, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.

Abstract

Rhabdoid tumours (RTs) are highly aggressive tumours of infancy, frequently localized in the central nervous system (CNS) where they are termed atypical teratoid/rhabdoid tumours (AT/RTs) and characterized by bi-allelic inactivation of the SMARCB1 tumour suppressor gene. In this study, by temporal control of tamoxifen injection in Smarcb1(flox/flox);Rosa26-Cre(ERT2) mice, we explore the phenotypes associated with Smarcb1 inactivation at different developmental stages. Injection before E6, at birth or at 2 months of age recapitulates previously described phenotypes including embryonic lethality, hepatic toxicity or development of T-cell lymphomas, respectively. Injection between E6 and E10 leads to high penetrance tumours, mainly intra-cranial, with short delays (median: 3 months). These tumours demonstrate anatomical, morphological and gene expression profiles consistent with those of human AT/RTs. Moreover, intra- and inter-species comparisons of tumours reveal that human and mouse RTs can be split into different entities that may underline the variety of RT cells of origin.

PMID:
26818002
PMCID:
PMC4738337
DOI:
10.1038/ncomms10421
[Indexed for MEDLINE]
Free PMC Article

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